General Approach for Machine Learning-Aided Design of DNA-Stabilized Silver Clusters
General Approach for Machine Learning-Aided Design of DNA-Stabilized Silver Clusters
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DOI：
10.1021/acs.chemmater.9b04040
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发表时间：
2020-01-14
影响因子：
8.6
通讯作者：
Gwinn, Elisabeth G.
中科院分区：
文献类型：
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作者：
Copp, Stacy M.;Swasey, Steven M.;Gwinn, Elisabeth G.
DNA模板银团簇（Ag-N-DNA）对于DNA模板序列的不同选择表现出宽范围的荧光颜色。虽然这些簇是有前途的生物传感器和生物标记物，但Ag-N-DNA的合理设计受到可能的DNA模板序列的巨大空间的挑战。最近的工作采用了在实验数据上训练的机器学习方法来设计新的DNA模板，用于选择Ag-N-DNA颜色，用于10碱基DNA寡聚体的特定情况。一个重要的未决问题是，这样的设计过程中开发的一个特定的生物聚合物模板长度是否适用于其他长度，不同数量和不同配置的集群成核位点。在这里，我们开发了一种灵活的设计方法，该方法建立在从2000多个10个碱基的DNA寡聚体的数据中学习的颜色相关的DNA碱基基序上。我们测试这种基于基序的设计模板范围从8个碱基到16个碱基长，其中序列空间的大小相差近5个数量级。实验数据表明，所有长度的设计链在600-660 nm的目标波长带中对Ag-N-DNA颜色具有选择性，这强烈表明针对一种模板长度学习的颜色选择性基序推广到其他长度。因此，基于基序的设计方法可能广泛适用于未来的Ag-N-DNA应用。
DNA-templated silver clusters (Ag-N-DNA) are known to exhibit a wide range of fluorescence colors for different choices of the DNA template sequence. While these clusters are promising biosensors and biomarkers, rational design of Ag-N-DNA is challenged by the huge space of possible DNA template sequences. Recent work employed machine learning methods trained on experimental data to design new DNA templates that select for Ag-N-DNA color, for the specific case of 10-base DNA oligomers. An important open question is whether such a design process developed for a specific biopolymer template length is applicable at other lengths, with different numbers and diverse configurations of cluster nucleation sites. Here, we develop a flexible design approach that builds on color-correlated DNA base motifs learned from data on more than 2000 10-base DNA oligomers. We test this motif-based design for templates ranging from 8 bases to 16 bases long, for which the sizes of the sequence spaces differ by nearly 5 orders of magnitude. The experimental data show that designed strands of all lengths are selective for Ag-N-DNA color in the target wavelength band of 600-660 nm, strongly suggesting that color-selective motifs learned for one template length generalize to other lengths. Thus, a motif-based design approach may be broadly suitable for future Ag-N-DNA applications.